The ultimate goal of these studies is to understand how exposing the skin of mice to ultraviolet radiation (UVR) leads to the production of suppressor T lymphocytes (Ts) that inhibit the rejection of UV-induced skin cancers. Considerable evidence suggests that the antigen presentation step of the immune response is the critical point at which UVR exerts its immunomodulatory effect. Therefore, these studies address the mechanism by which UVR alters the function of antigen presenting cells (APC) and the pathway by which altered APC function leads to Ts activation. The problem will be investigated using a model system of cutaneous immunity in which a contact sensitizing hapten (FITC) is used as the immunogen. We propose to test the following series of specific hypotheses concerning the sequence of events that leads to Ts induction: (1) DNA damage is the initiating event in Ts induction by UVR. (2) Epidermal cytokines are responsible for altered APC activity. (3) "UV- altered" APC interact with different subsets of T lymphocytes than normal APC, resulting in a modified pattern of lymphokine secretion. (4) The modified pattern of lymphokine secretion is responsible for Ts induction. As these hypotheses are tested, we will attempt to assess their relevance for the induction of Ts in the UV carcinogenesis system.